1 April 2010
In a recent issue of Journal of Alzheimer’s Disease, Zhang and colleagues presented interesting data concerning the cholinergic deficit in Alzheimer’s disease (AD) [1]. These results demonstrated decreases in the activity of acetylcholinesterase (AChE) and reduced mRNA levels of α4 and β2 nicotinic acetylcholine receptor (nAChR) subunits in peripheral blood of patients with AD in an elderly Chinese population. Although accumulating evidence indicates that changes in the AD brain may be reflected by alterations in the peripheral blood cells of AD patients, there are not, as yet, universally accepted biological tests for an unequivocal diagnoses of the disease. As such, an important aspect of this study was that these alterations might be used as supplementary markers for the diagnosis of AD. However, there are several points that merit discussion.
First, as stated in the article, the mean score of MMSE tests for AD patients was 10.25±5.77. Therefore, we understand that all of patients were moderate and severe stages. The natural history of AD has a broad spectrum considered as a presymptomatic stage during which a number of pathological events take place over many years, an early symptomatic or prodromal stage [amnestic-mild cognitive impairment (aMCI)] with cognitive and, at times, neuropsychiatric manifestations, and symptomatic mild, moderate, and severe stages. It should be noted that decline is faster in the moderate and severe stage related to the natural progression of AD. While hopes for reversibility of pathological changes target the early stages of AD (aMCI and mild stage) for disease modification, unfortunately, diagnosis of aMCI and mild stage AD is problematic in general practice [2].
Second, anticholinergic drug use increases with advanced age because of frequently emerging disorders such as chronic obstructive lung disease, overactive bladder, and irritable bowel syndrome. Unfortunately, there was no information about anticholinergic drugs taken from patients or control subjects in the published study. This is important due to the fact that it is known that acetylcholine effect is blocked by these drugs [3-5], and we think that increased acetylcoline may cause changes in AChE activity.
In conclusion, we suggestion that future studies assess aMCI and mild stage AD where the early initiation of cholinesterase inhibitors therapy may defer the progression of disease and may prolong survival time. For this reason, all physicians need a marker for the early stages of AD. Also, as indicated, the confounding effects of any anticholinergic drug is important to consider. The aspects would certainly provide insights into the future identification of candidates with diagnostic biomarkers in peripheral blood.
Mehmet Ilkin Naharci, MD
Gulhane School of Medicine, Department of Internal Medicine, Division of Geriatrics, Ankara, Turkey; Tel: +90-312-304 31 22, Fax: +90-312-304 31 03, Email: inaharci@gata.edu.tr
Huseyin Doruk, MD
Gulhane School of Medicine, Department of Internal Medicine, Division of Geriatrics, Ankara, Turkey
Ergun Bozoglu, MD
Gulhane School of Medicine, Department of Internal Medicine, Division of Geriatrics, Ankara, Turkey
References:
[1] Zhang LJ, Xiao Y, Qi XL, Shan KR, Pei JJ, Kuang SX, Liu F, Guan ZZ (2010) Cholinesterase activity and mRNA level of nicotinic acetylcholine receptors (α4 and β2 Subunits) in blood of elderly Chinese diagnosed as Alzheimer’s disease. J Alzheimer’s Dis 19, 849-858.
[2] Spar JE, La Rue A (2006) Dementia and Alzheimer disease. In Clinical Manual of Geriatric Psychiatry, Washington DC, eds. American Psychiatric Publishing, London, pp. 173-229.
[3] Buhling F, Lieder N, Ulrike C, Kühlmann UC, Waldburg N, Welte T (2007) Tiotropium suppresses acetylcholine-induced release of chemotactic mediators in vitro. Respir Med 101, 2386–2394.
[4] Matsui T, Kimura I, Kimura M (1990) Increase in the activities of plasma pseudocholinesterase dependent on the blood glucose level and its relation to the hypersensitivity to acetylcholine in striated muscles of KK-CAy mice with diabetes. Jpn J Pharmacol 54, 97-103.
[5] Pieper MP, Chaudhary NI, Park JE (2007) Acetylcholine-induced proliferation of fibroblasts and myofibroblasts in vitro is inhibited by tiotropium bromide. Life Sci 80, 2270-2773.
